Aldesleukin Imaging in Viewing Tumor Growth in Patients With Stage IV Melanoma Receiving Ipilimumab or Pembrolizumab Therapy

Inclusion Criteria:

* Pathologic proof of stage IV melanoma (pathology report confirmation) with plans to initiate therapy with ipilimumab or pembrolizumab according to Food and Drug Administration (FDA) approved guidelines, with multiple lesions such that

  * Two of these lesions are in the same organ and at least one of these two lesions is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either intravenous (IV) contrast enhanced computed tomography (CT) or CT component of positron emission tomography (PET)/CT OR
  * Three of these lesions are in different organs and at least one of these 3 lesions is measurable by RECIST 1.1 using either IV contrast enhanced CT or CT component of PET/CT
* Patient eligible for and will be receiving ipilimumab or pembrolizumab as standard of care therapy
* Absolute neutrophil count (ANC) \>= 1500 mL
* Hemoglobin (Hgb) \> 10 g/dL
* Platelets (PLT) \>= 50,000 mL
* Aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN)
* Alkaline phosphatase =\< 3 x ULN; up to 5 x allowed for patients with liver metastases
* Ability to provide informed consent
* Willingness to return to Mayo Clinic Rochester for follow-up
* Life expectancy \>= 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* For women of childbearing potential, a negative serum pregnancy test =\< 7 days prior to registration
* Willingness to participate in mandatory imaging studies as well as provide mandatory blood samples for correlative research
* Tumor accessible for biopsy

Exclusion Criteria:

* Uncontrolled or current infection
* Known allergy to 99mTc-HYNIC-IL2 or components
* Any of the following prior therapies with interval since most recent treatment:

  * Chemotherapy =\< 3 weeks prior to registration
  * Biologic therapy =\< 3 weeks prior to registration
  * Radiation therapy =\< 3 weeks prior to registration
* Failure to recover from side effects of prior chemotherapy or surgery
* Any of the following:

  * Pregnant women
  * Nursing women
  * Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.)